Abstract
BACKGROUND: The presence of lymph node metastases in patients with urothelial carcinoma (UC) plays a pivotal role in disease management and prognosis. Patients with locally advanced irresectable or clinically node-positive UC are often considered ineligible for surgery due to the extent of affected lymph nodes. Long term remission or even cure may be achieved in a subset of patients who experience response to systemic induction therapy and consolidative locoregional treatment. OBJECTIVE: To assess the pathological response to preoperative systemic induction therapy followed by radical surgery in patients with locally advanced irresectable or clinically node-positive UC. METHODS: Searches were performed until September 2023 in 5 databases (EMBASE, MEDLINE, Web-of-Science, Cochrane and Pubmed Publisher). Studies including patients with cT4bNxM0/cTxN1-3M0 UC, treated with induction chemotherapy or non-chemo induction therapy followed by radical surgery, were selected. The primary outcome was the pathological complete response (pCR) rate, i.e., the proportion of patients without residual disease in the surgical resection specimen (ypT0N0). Secondary outcomes included overall and cancer-specific survival (OS, CSS). RESULTS: Fourteen studies were included, representing 5715 patients. Two studies reported on non-chemo induction therapy. The reported pCR rate in patients receiving induction chemotherapy varied from 9% to 27% compared to 25% after induction immunotherapy. The 5-year OS and CSS after induction chemotherapy and radical surgery ranged from 25 to 34% and 30 to 49%. CONCLUSION: Systemic induction therapy in patients with locally advanced irresectable or clinically node-positive UC resulted in modest pCR rates. Due to considerable heterogeneity between studies, no direct comparison on the efficacy of induction therapy regimens was possible.